Diet Rich in Simple Sugars Promotes Pro-Inflammatory Response via Gut Microbiota Alteration and TLR4 Signaling

Abstract

Diet is a strong modifier of microbiome and mucosal microenvironment in the gut. Recently, components of western-type diets have been associated with metabolic and immune diseases. Here, we studied how high-sugar diet (HSD) consumption influences gut mucosal barrier and immune response under steady state conditions and in a mouse model of acute colitis. We found that HSD significantly increased gut permeability, spleen weight, and neutrophil levels in spleens of healthy mice. Subsequent dextran sodium sulfate administration led to severe colitis. In colon, HSD significantly promoted neutrophil infiltration and increased the levels of IL-6, IL-1β, and TNF-α. Moreover, HSD-fed mice had significantly higher abundance of pathobionts, such as Escherichia coli and Candida, in fecal samples. Although germ-free mice colonized with microbiota of conventionally reared mice that consumed different diets had equally severe colitis, mice colonized with HSD microbiota showed markedly increased infiltration of neutrophils to the gut. The induction of colitis in Toll-like receptor 4 (TLR4)-deficient HSD-fed mice led to significantly milder colitis than in wild-type mice. In conclusion, our results suggested a significant role of HSD in disruption of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seemed to be highly influenced by resident potentially pathogenic microbiota or metabolites via the TLR4 signaling pathway.

Insufficient Physical Fitness and Deficits in Basic Eating Habits in Normal-Weight Obese Children Are Apparent from Pre-School Age or Sooner

“…Regular consumption of sweet confectionery in the long term is associated with increasing of pro-inflammatory markers such as C-reactive protein (CRP), interleukin 6 (IL-6) or tumor necrosis alpha (TNF alpha) [68]. In animal studies, a high-saccharide diet led to disruption of barrier integrity, greater gut permeability with a subsequent increasing level of pro-inflammatory markers IL-6, TNF alpha [69]. Further, in human studies, the elevated level of IL-6 or C-reactive protein was positively associated with physical inactivity and negatively related to the amount of leisure time dedicated to physical activity in children and adults [70][71][72].…”

Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions

“…However, while the former increases proinflammatory tuning in gut monocytes the latter worsens the gut barrier function. In both cases, however, interactions between diet and microbiota are necessary for this deleterious effects as they fail to appear in germ-free condition or after transfer of the microbiota to naive mice [16,17].…”

Glucose as a Potential Key to Fuel Inflammation in Rheumatoid Arthritis

“…On the other hand, simple and digestible carbohydrates (e.g., sucrose, fructose, and glucose) are also indicated to modulate microbial diversity. Furthermore, they would impair gut permeability [ 68 , 69 ]. Fajstova et al showed that a diet rich in simple sugars (high-sugar diet or HSD) induced an alteration in gut microbial composition and inflammatory immune responses in mice and that the HDS-fed mice showed increased severity of experimental colitis [ 68 ].…”

“…Furthermore, they would impair gut permeability [ 68 , 69 ]. Fajstova et al showed that a diet rich in simple sugars (high-sugar diet or HSD) induced an alteration in gut microbial composition and inflammatory immune responses in mice and that the HDS-fed mice showed increased severity of experimental colitis [ 68 ]. In the field of autoimmune diseases, it has been reported that dietary free sugar intake was associated with the disease activity of systemic lupus erythematosus (SLE) [ 69 ], which indicates a possible role for sugar intake in SLE and other autoimmune rheumatic diseases.…”